Abnormal uterine bleeding diagnoses and care following COVID-19 vaccination.

BACKGROUND: There is evidence suggesting that COVID-19 vaccination may be associated with small, transitory effects on uterine bleeding, possibly including menstrual timing, flow, and duration, in some individuals. However, changes in health care seeking, diagnosis, and workup for abnormal uterine bleeding in the COVID-19 vaccine era are less clear. OBJECTIVE: This study aimed to assess the impact of COVID-19 vaccination on incident abnormal uterine bleeding diagnosis and diagnostic evaluation in a large integrated health system. STUDY DESIGN: Using segmented regression, we assessed whether the availability of COVID-19 vaccines was associated with changes in monthly, population-based rates of incident abnormal uterine bleeding diagnoses relative to the prepandemic period in health system members aged 16 to 44 years who were not menopausal. We also compared clinical and demographic characteristics of patients diagnosed with incident abnormal uterine bleeding between December 2020 and October 13, 2021 by vaccination status (never vaccinated, vaccinated in the 60 days before diagnosis, vaccinated >60 days before diagnosis). Furthermore, we conducted detailed chart review of patients diagnosed with abnormal uterine bleeding within 1 to 60 days of COVID-19 vaccination in the same time period. RESULTS: In monthly populations ranging from 79,000 to 85,000 female health system members, incidence of abnormal uterine bleeding diagnosis per 100,000 person-days ranged from 8.97 to 19.19. There was no significant change in the level or trend in the incidence of abnormal uterine bleeding diagnoses between the prepandemic (January 2019-January 2020) and post-COVID-19 vaccine (December 2020-December 2021) periods. A comparison of clinical characteristics of 2717 abnormal uterine bleeding cases by vaccination status suggested that abnormal bleeding among recently vaccinated patients was similar or less severe than abnormal bleeding among patients who had never been vaccinated or those vaccinated >60 days before. There were also significant differences in age and race of patients with incident abnormal uterine bleeding diagnoses by vaccination status (Ps<.02). Never-vaccinated patients were the youngest and those vaccinated >60 days before were the oldest. The proportion of patients who were Black/African American was highest among never-vaccinated patients, and the proportion of Asian patients was higher among vaccinated patients. Chart review of 114 confirmed postvaccination abnormal uterine bleeding cases diagnosed from December 2020 through October 13, 2021 found that the most common symptoms reported were changes in timing, duration, and volume of bleeding. Approximately one-third of cases received no diagnostic workup; 57% had no etiology for the bleeding documented in the electronic health record. In 12% of cases, the patient mentioned or asked about a possible link between their bleeding and their recent COVID-19 vaccine. CONCLUSION: The availability of COVID-19 vaccination was not associated with a change in incidence of medically attended abnormal uterine bleeding in our population of over 79,000 female patients of reproductive age. In addition, among 2717 patients with abnormal uterine bleeding diagnoses in the period following COVID-19 vaccine availability, receipt of the vaccine was not associated with greater bleeding severity.

Atypical Placental Site Nodules within the Diverticulum of the Uterine Incision, a Rare Gestational Trophoblastic Disease Misdiagnosed as Intrauterine Residue: A Case Report.

Atypical placental site nodule (APSN) is a rare benign gestational trophoblastic disease (GTD). It is a tumor-like transformation that has a certain probability of developing into a placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT). Because of its atypical clinical presentation, it is difficult to diagnose and susceptible to misdiagnosis highly, thus delaying the patient's condition. We report a scarce case of atypical nodules at the placental site of the uterine incision diverticulum in a 35-year-old female, who was irregular vaginal bleeding after a cesarean Sect. 2 years. She was diagnosed by several local hospitals with intrauterine residue and was given a variety of Traditional Chinese Medicine (TCM) orally, but the symptoms of irregular vaginal bleeding have not been alleviated. After being transferred to several hospitals, she went to Hubei Maternal and Child Health Hospital for treatment. Under the condition of excluding the second pregnancy, she underwent hysteroscopic resection of lesions and laparoscopic repair of uterine incision diverticulum. The pathological diagnosis after the operation suggested that the focus at the uterine incision was an atypical placental nodule that invaded the myometrium of the uterus. The operation completely removed the focus, and then the patient was followed up every 3 months in the first postoperative year, then every 6 months up to 3 years, and then annually thereafter up to 5 years, and then maybe every 2 years thereafter. The patient's condition was quickly controlled, and the prognosis was good.

Postmenopausal bleeding after COVID-19 vaccination.

BACKGROUND: There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination. OBJECTIVE: This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination. STUDY DESIGN: For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology. RESULTS: In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination. CONCLUSION: Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.

Pulmonary embolism after diagnostic curettage in patient with adenomyosis and hysteromyoma: A case report and brief review of literature.

RATIONALE: Pulmonary embolism (PE) is a common cause of cardiovascular death whose major acquired risk factors include postoperative states, pregnancy, malignancy, and age. We report a case of PE that occurred after diagnostic curettage for abnormal uterine bleeding, with a medical history of adenomyosis and hysteromyoma. PATIENT CONCERNS AND DIAGNOSES: A 31-year-old Han Chinese female was referred to our hospital with menstrual disorders, increased menstrual flow, and severe anemia. After admission, the patient was treated with a blood transfusion, iron supplementation, and erythropoietin, and diagnostic curettage was performed the following day. On the first postoperative day, the patient developed pulmonary embolism with dyspnea and fever diagnosed by CT pulmonary angiography and significantly elevated D-dimer. INTERVENTIONS AND OUTCOMES: Molecular weight heparin was administered for PE for 2 weeks, dyspnea was relieved significantly after 2 days of treatment and the uterine bleeding did not increase; and gonadotropin-releasing hormone agonists were administered for adenomyosis after 1 week of anticoagulant therapy to reduce bleeding. We followed up for 6 months, and the patient had no recurrence of thrombosis and uterine bleeding had improved. CONCLUSION: We speculate that the occurrence of pulmonary embolism was closely related to adenomyosis, hysteromyoma, and curettage in this patient. Treating the presence of both menstrual bleeding and thromboembolism is challenging, and careful management is necessary to avoid therapeutic contradictions.

Abnormal uterine bleeding: an insidious presentation.

An adolescent was referred to the emergency department due to abnormal uterine haemorrhages in the previous 2 months, associated with dizziness in the last month. At observation, she was haemodynamically stable, with good clinical impression, but evident mucocutaneous pallor. Full blood count confirmed a severe anaemia (haemoglobin 47 g/L). She received red blood cell transfusion (10 mL/kg) and started oral oestradiol. She was discharged, with oral oestradiol and oral iron supplementation. Two weeks later, she started treatment with oestradiol and progestin. The patient had a good recovery, without new similar episodes.

The effect of progesterone supplementation in women with threatened miscarriage on fetal fraction in non-invasive prenatal testing: A matched case-control study.

AIM: To evaluate the effect of progesterone use on fetal fraction (FF) in non-invasive prenatal testing (NIPT) due to the threat of first trimester miscarriage. METHODS: This case control study included the pregnant who were referred to our clinic for non-invasive prenatal testing. The patients were categorized into three groups: Pregnant women with vaginal bleeding and using progesterone, pregnant women with vaginal bleeding and not using progesterone, and pregnant women without bleeding. The groups were formed by matching gestational week. Women with multiple pregnancy, BMI (body mass index) ≥25, abnormal fetal karyotype, and chronic disease were excluded from the study. Maternal characteristics, FF of the NIPT were recruited from the computer based medical records. RESULTS: A total of 10,275 NIPT tests were performed during the study period. 3% of the patients (n = 308) were found at risk of miscarriage. 100 patients with a vaginal bleeding and 50 control patients were matched. The median value of the fetal fraction ratio was found to be 6.55 in pregnant women without vaginal bleeding, 7.05 in pregnant women who had vaginal bleeding and using progesterone, and 7.3 in pregnant women who had vaginal bleeding and did not use progesterone. Although the fetal fraction ratio was found to be higher in pregnant women with vaginal bleeding and lower in progesterone users, this situation could not reach the level of statistical significance (p = 0.351). CONCLUSIONS: The fetal fraction rate in maternal blood is not affected in pregnant women who use progesterone due to vaginal bleeding in early gestational weeks.

Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.

Phyto-progestins for the treatment of abnormal uterine bleeding without organic cause in women at high risk for breast cancer and breast cancer survivors: a prospective, pilot study.

OBJECTIVES: Some plants, such as Dioscorea Villosa (DV), Vitex Agnus Castus (VAC) and Turnera diffusa (D) have some 'progesterone-like' properties. We have investigated their simultaneous administration in breast cancer (BC) survivors or carriers of specific genetic mutations that can increase the risk of developing BC suffering from abnormal uterine bleeding without organic cause. METHODS: Women with irregular cycles in terms of length (interval between ≤ 24 or ≥ 38 days) without a uterine organic disease (polyps, adenomyosis, fibroids, hyperplasia/malignancy) were included. A daily diary of bleeding, questionnaires about health-related quality of life (Short Form 36) and menstrual psychophysical well-being (PGWB-1) and the Greene Climacteric Scale (GCS) (in women older than 40 years old) questionnaire were used. The presence of some premenstrual syndrome (PMS) symptoms was also evaluated. RESULTS: In the analyzed group of women (n = 15), all experienced a regularization of the menstrual cycles, with a mean duration in the three months of use of 27.1 ± 3.2 days, with a significant reduction of menstrual pain (p = 0.02) and flow (p = 0.02) intensity. Women with PMS (7/15) reported an impovement in depression, headache and abdominal pain scores (p < 0.05). No specific deterioration of different questionnaires evaluated during treatment were observed. General satisfaction with the treatment was 6.8 ± 0.3/10 on a 10 point. CONCLUSIONS: A combination of DV, VAC and D could be a promising candidate to treat menstrual irregularities without an organic cause, with a significant reduction of menstrual pain and flow intensity and possible additional benefits in PMS symptoms treatment in women at genetic risk for BC and BC survivors.

Combined Metabolite Analysis and Network Pharmacology to Elucidate the Mechanisms of Therapeutic Effect of Melastoma dodecandrum Ellagitannins on Abnormal Uterine Bleeding.

The abnormal uterine bleeding (AUB) is complex and usually leads to severe anemia. Melastomadodecandrum (MD) is clinically used for the treatment of metrorrhagia bleeding. The MD ellagitannins (MD-ETs) had been evidenced being effective at hemorrhage, and exerts biological activities upon their metabolites including ellagic acid and urolithins. In this study, the blood-permeated metabolites from theMD-ETs were analyzed using LC-MS approach, and 19 metabolites including ellagic acid and urolithin A derivatives were identified. Furthermore, a network pharmacology analysis including the target prediction analysis, AUB target analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal the relationships between "metabolites-targets-pathways", which was further verified by molecular docking analysis. The results showed that methyl ellagic acid, urolithin A and isourolithin A produced from MD-ETs can be absorbed into the blood, and might act on the core targets of VEGFA, SRC, MTOR, EGFR and CCND1. And the hemostatic effects were exerted through PI3K-Akt, endocrine resistance and Rap 1 signaling pathways. These results implied the potential effective constituents and action mechanism of MD-ETs in the therapy of AUB, which will promote the application of MD-ETs as natural agent for the treatment of gynecological bleeding diseases.

Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

Successful treatment of radiation-induced vaginal soft tissue radionecrosis with HBO2.

Introduction: Radiation therapy to the pelvis can result in radiation-induced vaginal soft tissue necrosis. This significantly impacts quality of life. Studies evaluating the efficacy of HBO2 are limited. Methods: In this retrospective report, we reviewed the medical records of patients treated with once-daily HBO2 for radiation-induced vaginal soft tissue necrosis. We included females between the ages of 18 to 90 with history of pelvic cancer treated with radiotherapy and resultant soft tissue radionecrosis. Data collected included age, comorbid disease, cancer type, radiation dose, HBO2 treatment pressure, time, and total treatments. Primary outcome was improvement of radionecrosis; secondary outcomes were improvement of pelvic pain, reduction in need for analgesia, and improvement of vaginal bleeding. Results: Seven patients were identified, of which six received HBO2. One patient had a vaginal fistula. Four patients had documented improvement of radionecrosis. Four out of five patients with pelvic pain had resolution of their pain, with two patients no longer requiring opioid analgesia. Two patients who presented with vaginal bleeding showed improvement with one resolved and one significantly decreased requiring no further hospitalization or transfusion. One patient experienced no documented improvement in any of the measured outcomes. Conclusion: In this case series, five out of six (83%) patients treated with HBO2 for radiation-induced vaginal necrosis improved in at least one outcome measure. While the sample size is small, these results add to the data available that supports the use of HBO2 in suitable candidates without contraindications who have symptoms related to radiation-induced vaginal soft tissue necrosis.

Women with Anemia Refractory to Oral Iron Treatment Following Bariatric Surgery: a Short-Term Analysis.

INTRODUCTION: Iron deficiency and anemia are common after bariatric surgery. Women have a higher risk of developing such long-term complications. Though oral supplementation is indicated, intravenous iron therapy is required in some cases. METHODS: This retrospective study included patients who underwent bariatric surgery between 2012 and 2018. Postoperative anemia patients receiving parental iron therapy were assessed during the first 24 months. Their baseline characteristics, surgery type, and laboratory test results were analyzed. A follow-up analysis included a subgroup of women with and without gynecological disorders. Patients with vitamin B12 or folic acid deficiencies were excluded. RESULTS: Six hundred eleven (63.3%) met the inclusion criteria: 525 underwent gastric bypass, of which 79.6% were women. Overall, postoperative anemia was 28.9% (24.5% related to gastric bypass), especially among women (84%). Anemia refractory to oral iron therapy was observed in 12.9% of patients. All the patients requiring iron infusions (n = 54) were women, and half of them (51.8%) reported abnormal uterine bleeding. Postsurgical hemogram values were significantly lower in patients with abnormal uterine bleeding (despite the same number of infusions) than in those without gynecological disorders; 89.2% of these women had preoperative anemia. CONCLUSION: Anemia is frequent in bariatric surgery patients despite supplementation. Women undergoing gastric bypass with a history of gynecological disorders are prone to require more iron infusions. Consulting with the patient about a higher risk is important, and probably knowing the plan or including the opinion of an OBGYN to determine as a team the assessment, treatment, and prognosis.

The Prevalence of Dietary Supplements That Claim Estrogen-like Effects in Japanese Women.

Recently, adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of dietary supplements containing Pueraria mirifica, have been reported in Japan. P. mirifica contains phytoestrogens, such as deoxymiroestrol and miroestrol. Therefore, we investigated the use of supplements that claim to have estrogen-like effects (i.e., estrogen-like supplements) in Japanese women aged from 15 to 69 years old in an online survey. The prevalence of estrogen-like supplement use was 5%, accounting for approximately 15% of the sample, including ex-users. The majority of the users were in their 40s and 50s, mainly using these supplements for the treatment of menopausal symptoms. In contrast, the younger generation mainly used them for beauty purposes, such as weight loss, mastogenic effects, and skin care. Many of them visited a clinic or took medicines for menstrual-related troubles. In all age groups, soybeans/isoflavones were the most commonly used, followed by equol and placenta. Participants in their teens and 20s also used P. mirifica. Among them, 16.2% had experienced adverse events, including irregular vaginal bleeding, breast swelling and pain, and heavy menstruation. In conclusion, estrogen-like supplement use is associated with adverse events; thus, it is necessary to pay attention to the use of these supplement. Furthermore, because the purpose of use differs depending on generation, caution according to each generation is necessary.

Efficacy of Qiancao () and Haipiaoxiao (), a traditional Chinese herb pair, on abnormal uterine bleeding in rats with incomplete abortion.

OBJECTIVE: To investigate the most effective weight ratio of Qiancao () and Haipiaoxiao () used to produce decoction for the treatment of abnormal uterine bleeding (AUB) in rats with incomplete abortion, and to study the possible mechanism. METHODS: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao () and Haipiaoxiao () were observed. RESULTS: Statistical analysis revealed that the most effective weight ratio of Qiancao () and Haipiaoxiao () to treat AUB in this study was 2∶1. CONCLUSION: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao () and Haipiaoxiao () on AUB.

[Simultaneous determination and pharmacokinetic study of five compounds from total extract of Clinopodium chinense in abnormal uterine bleeding rat plasma by UPLC-MS/MS].

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 µg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

[Clinical random trial of thumbtack needling therapy for analgesia after cesarean section].

OBJECTIVE: To observe the analgesic effect of thumbtack needling therapy and the quality of life in puerpera underwent cesarean section. METHODS: One hundred and thirty-five puerpera underwent cesarean section were randomly divided into a medication group, a sham-thumbtack needling group and a thumbtack needling group, 45 cases in each group. In the medication group, the patient control analgesia (PCA) was given. In the thumbtack needling group, on the base of the regimen as the medication group, acupuncture with thumbtack needles was applied to lower abdominal point (Extra), Zusanli (ST36), Sanyinjiao (SP6), Geshu (BL17), Shenshu (BL23) and Dachangshu (BL25). The needles were retained for 48 hours. During the needle retaining, the sites with the needle embedded were pressed and kneaded for 3 times, 1 min each time, at the interval of 4 to 12 h. In the sham-thumbtack needling group, the sham-thumbtack needles were used; the acupoint selection, operation and treatment course were all the same as the thumbtack needling group. The visual analogue scale (VAS) scores of incision pain and ute-rine contraction pain, the incidence of postoperative adverse reactions, the amount of vaginal bleeding and milk amount in lactation were observed at each time point after the operation separately in each group. RESULTS: Compared with the medication group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 8, 12, 24 and 48 h after operation (P<0.05), the lactation score was increased in 24 to 48 h after operation (P<0.05) in both the sham-thumbtack needling group and thumbtack needling group. Compared with the sham-thumbtack needling group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 24 and 48 h after operation (P<0.05) in the thumbtack needling group. Compared with those from 2 to 24 h after operation, the vaginal bleeding amount was decreased and the lactation score increased from 24 to 48 h after operation (P<0.05) in all of the three groups. CONCLUSION: The conventional PCA combined with thumbtack needling therapy obtained better analgesic effects on incision dynamic pain and uterine contraction pain in patients after cesarean section as compared with either the simple PCA or the combined treatment with sham-thumbtack needling and medication, and both the thumbtack needling and the sham-thumbtack needling therapy can increase the milk amount of lactation from 24 to 48 h after operation.

The effects of magnesium supplementation on abnormal uterine bleeding, alopecia, quality of life, and acne in women with polycystic ovary syndrome: a randomized clinical trial.

BACKGROUND: Abnormal uterine bleeding (AUB), alopecia, low quality of life, and acne are considered as complications of polycystic ovary syndrome (PCOS). We hypothesized that magnesium supplementation would yield beneficial effects on PCOS related complications. OBJECTIVE: To examine the effects of magnesium supplementation on AUB, alopecia, quality of life, and acne. METHODS: In this parallel randomized clinical trial, we randomly assigned 64 women with PCOS to the magnesium group (n = 32) or placebo group (n = 32) for 10 weeks. AUB, alopecia, quality of life, and acne were assessed by the International Federation of Gynecology and Obstetrics criterion, the Sinclair Scale, the Health Survey Quality of Life Questionnaire, and the Global Acne Grading System, respectively. This randomized clinical trial was registered at IRCT.ir (IRCT20130903014551N9). RESULTS: Magnesium supplementation significantly improved the components of quality of life including physical functioning (p = 0.011), role limitations due to physical health (p = 0.012), role limitations due to emotional problems (p < 0.001), energy/fatigue (p = 0.005), emotional wellbeing (p < 0.001), social functioning (p = 0.002), general health (p = 0.013), and total quality of life (p < 0.001), compared with placebo. No significant effect was observed on acne, alopecia, and AUB. CONCLUSION: Magnesium supplementation in women with PCOS had a significant positive effect on improving total quality of life. TRIAL REGISTRATION: This randomized clinical trial was registered at IRCT.ir on 2020-10-18 (Registration Code: IRCT20130903014551N9 ).

The effect of preoperative oral carbohydrate on the time to colostrum and amount of vaginal bleeding after elective cesarean section.

OBJECTIVE: To investigate the effect of oral carbohydrate at 2 h before elective cesarean section on postoperative recovery indicators such as the time to colostrum and vaginal bleeding. METHODS: Women undergoing elective cesarean section under spinal-epidural anesthesia, aged 20-40 years, with a body mass index (BMI) of 19-30 kg/m2 and an American Society of Anesthesiology (ASA) score of II were randomized to the oral carbohydrate group (the OC group), the oral placebo group (the OP group), or the control group (the C group). The OC group underwent oral carbohydrate preloading (300 mL/bottle), the OP group orally consumed 300 mL of distilled water, and the C group was forbidden from drinking or eating on the day of the operation. The time to colostrum, vaginal bleeding, time to exhaust, and complications were recorded. RESULTS: A total of 38 participants in the OC group, 37 in the OP group, and 37 in the C group completed the study. Compared with the OP group and the C group, the OC group produced colostrum significantly earlier, had a lower amount of 24-h vaginal bleeding, and had a higher 24-h consumption of analgesics. Compared with OP and OC groups, the C group took longer to exhaust. No significant intergroup difference was observed for any other indicator. CONCLUSION: Oral carbohydrates loading 2 h before elective cesarean section significantly reduces the time to produce colostrum and the amount of vaginal bleeding, which contributes to postoperative recovery.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Clinical Features, Management and Maternal-Infant Prognosis in Patients with Complete Uterine Rupture in the Second and Third Trimester of Pregnancy.

Objectives: Our study aimed to investigate the clinical features, management, and maternal-infant prognosis in patients with complete uterine rupture in the second and third trimester of pregnancy. Methods: A total of 15 patients with complete uterine rupture in their second and third trimester of pregnancy who were admitted to our hospital between January 2012 and December 2020 were included in our study. The patients enrolled were divided into the scar group (11 patients) and the non-scar group (4 patients) according to the existence or absence of a uterine scar. The general data, clinical characteristics and follow-up results in the 2 groups were compared. Results: There was no significant difference in age, pregnancy duration or delivery cycle between the 2 groups (P > .05). The incidence of original scar rupture in the scar group was significantly higher than in the non-scar group (P > .05). No significant difference was found in clinical characteristics between the scar and the non-scar groups (P > .05). The most common clinical features included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. A total of 3 patients were misdiagnosed as having surgical disease. After completing relevant examinations, the uterine rupture was repaired surgically; the patients were discharged after blood transfusion, and their condition resolved. In all, 3 patients in the non-scar group and 1 patient in the scar group were transferred to the intensive care unit (ICU). All 15 patients were discharged after treatment. Follow-up was completed by all patients for 12 to 36 months, with an average follow-up time of 23.09 ± 2.19 months. Of the 15 patients, 2 underwent induced abortion after 24 months due to unplanned pregnancy. A 5-minute Apgar score of ≤7 in the scar group was higher than that in the non-scar group, but the difference was not statistically significant (P > .05). Perinatal mortality in the 15 patients was 40.00% (6/15). Conclusion: The most common clinical features in patients with complete uterine rupture in the second and third trimester of pregnancy included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. In addition, a remarkably worse maternal-infant prognosis was seen in patients with complete uterine rupture in the second and third trimester of scarless pregnancy compared with patients with complete uterine rupture in the second and third trimester of scarred pregnancy.